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Uveitis, a complex ocular disorder with numerous etiologies, can result from infection, autoimmune, and various physicochemical and mechanical injury factors. The treatment of this disease is difficult, and failure to receive timely and effective treatment can often lead to blindness. With the deepening of people's understanding of uveitis and its related mechanisms, various new sustained-release drug delivery systems for uveitis have been studied. However, due to the existence of various anatomical and physiological barriers in the eye, there are multiple obstacles to the sustained release treatment of uveitis. In this paper, the main research results in this field in recent years are reviewed, and the innovations and limitations of various new sustained-release drug delivery systems are discussed in order to provide new ideas for the sustained-release drug delivery treatment of uveitis in the future. These new sustained-release drug delivery systems will help to completely change the traditional treatment mode of uveitis with side effects and poor compliance in the future, bringing longer targeted sustained release and less toxic reactions.
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Objective:To study the clinical significance of alveolar-arterial oxygen gradients (P A-aO 2) for late preterm and full-term infants with acute respiratory distress syndrome (ARDS). Methods:From January 2020 to June 2022, infants (gestational age ≥34 weeks) diagnosed with ARDS were admitted to the Neonatology Department of our hospital. The infants were assigned into the invasive group and the non-invasive group according to the ventilation mode. The infants with the same gestational age and diagnosed with neonatal wet lung were assigned into the control group. P A-aO 2 levels within 1 h after birth were compared among the three groups. The correlation of P A-aO 2 with ARDS, ventilation mode and duration were studied. Receiver operating characteristic (ROC) curve was used to determine the predictive value of P A-aO 2 within 1 h after birth for ARDS and the need of invasive ventilation. Results:A total of 36 cases were enrolled in the invasive group, 19 cases in the non-invasive group and 50 cases in the control group. Within 1 h after birth, P A-aO 2 in the invasive group was significantly higher than the non-invasive group and the control group ( P<0.05), and the non-invasive group higher than the control group ( P<0.05). Correlation analysis showed that P A-aO 2 within 1 h after birth in the invasive group was positively correlated with the duration of invasive ventilation and total mechanical ventilation ( r=0.601, P<0.001; r=0.504, P=0.002); P A-aO 2 before successful withdrawal of invasive ventilation was not correlated with subsequent non-invasive ventilation duration; and no correlation existed between P A-aO 2 within 1 h after birth and the duration of non-invasive ventilation in the non-invasive group. The area under the ROC curve for P A-aO 2 within 1 h after birth to predict ARDS was 0.875, with a sensitivity of 87.3% and a specificity of 72.0% at a cutoff value of 50.0 mmHg. The area under the ROC curve for predicting the need for invasive ventilation in infants with ARDS was 0.851, with a sensitivity of 80.0% at a cutoff value of 73.3 mmHg and a specificity of 75.0%. Conclusions:Late preterm and full-term infants have a higher risk of ARDS at P A-aO 2>50.0 mmHg within 1 h after birth. Infants with ARDS are more likely to require invasive ventilation if P A-aO 2>73.3 mmHg. The higher the level of P A-aO 2, the longer the duration of invasive ventilation and total duration of mechanical ventilation.
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ObjectiveTo investigate the mechanism of Jiedu Huoxue prescription in promoting the reendothelialization of injured vessels by regulating the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3）/cysteine-aspartic acid protease （Caspase）-1-mediated pyroptosis. MethodA rat model of injured thoracic aorta was established by balloon injury， and 36 rats were assigned into shame surgery， model， low-， medium-， and high-dose Jiedu Huoxue prescription， and atorvastatin calcium tablet groups. The injured aortic segment was collected 28 days after surgery. Hematoxylin-eosin （HE） staining and Evans blue staining were conducted to reveal the changes of vascular structural morphology and the reendothelialization of blood vessels， respectively. The enzyme-linked immunosorbent assay （ELISA） was employed to determine the levels of tumor necrosis factor-α （TNF-α）， intercellular adhesion molecule-1 （ICAM-1）， interleukin （IL）-1β， and nitric oxide （NO） in the serum. Western blotting was employed to determine the expression of endothelial nitric oxide synthase （eNOS）， NF-κB p65， phospho-NF-κB p65 （p-NF-κB p65）， NLRP3， and Caspase-1 in the vascular tissue. ResultThe model group showed thickened endovascular membrane， proliferation and disarrangement of smooth muscle cells of the artery wall， obvious inflammatory cell infiltration， and narrowed luminal area. Jiedu Huoxue prescription and atorvastatin calcium tablets mitigated the pathological changes of the thoracic aorta in different degrees. After balloon injury， the endothelial coverage rate of the model group decreased significantly， while Jiedu Huoxue prescription and atorvastatin calcium tablets increased the reendothelialization rate （P<0.05）. Compared with the shame surgery group， the model group showed elevated levels of TNF-α， ICAM-1， and IL-1β （P<0.01） and lowered NO level （P<0.01） in the serum. In addition， the model group presented down-regulated protein level of eNOS （P<0.01） and up-regulated phosphorylation of pyroptosis-associated proteins NLPR3， Caspase-1， and NF-κB p65 in the vascular tissue （P<0.05， P<0.01）. Compared with the model group， Jiedu Huoxue prescription and atorvastatin calcium tablets lowered TNF-α， ICAM-1， and IL-1β levels （P<0.05， P<0.01） and elevated the NO level in the serum （P<0.05， P<0.01）. Moreover， the drugs up-regulated the expression of eNOS （P<0.01） and down-regulated the expression of NLRP3， Caspase-1， and NF-κB p65 （P<0.05， P<0.01） in the vascular tissue. ConclusionJiedu Huoxue prescription can promote the reendothelialization and inhibit the intimal hyperplasia of vessels after balloon injury by regulating the NF-κB/NLRP3/Caspase-1 pathway to inhibit pyroptosis and reduce endothelial inflammatory injury.
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@#The human gut microbiota regulates many host pathophysiological processes including metabolic, inflammatory, immune and cellular responses. In recent years, the incidence and mortality of lung cancer have increased rapidly, which is one of the biggest challenges in the field of cancer treatment today, especially in non-small cell lung cancer. Animal models and clinical studies have found that the gut microbiota of non-small cell lung cancer patients is significantly changed compared with the healthy people. The gut microbiota and metabolites can not only play a pro-cancer or tumor suppressor role by regulating immune, inflammatory responses and so on, but also be related with radiotherapy and chemotherapy of non-small cell lung cancer and the resistance of immunotherapy. Therefore, gut microbiota and related metabolites can be both potential markers for early diagnosis and prognosis in patients with non-small cell lung cancer and novel therapeutic targets for targeted drugs. This study will review the latest research progress of effect of gut microbiota on non-small cell lung cancer, and provide a new diagnosis and treatment ideas for non-small cell lung cancer.
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Objective:To investigate the clinical efficacy of insulin degludec/insulin aspart on type 2 diabetes mellitus in patients with poor efficacy of oral hypoglycemic drugs.Methods:A total of 100 patients with type 2 diabetes mellitus in Tianfu Hospital of Chongqing Energy Investment Health Industry Company Limited from August 2020 to August 2021 were included in this study. They were randomly assigned to receive either insulin degludec/insulin aspart combined with Metformin (observation group, n = 50) or nsulin aspart 30 injection and Metformin (control group, n = 50). All patients were treated for 3 months. Changes in fasting plasma glucose level, 2-hour postprandial glucose level , and HbAlc after treatment relative to those before treatment as well as clinical efficacy were determined in each group. Results:Forty-eight patients in the observation group and forty-six patients in the control group completed the course of treatment. Fasting blood glucose level and 2-hour postprandial glucose level in the observation group were (6.24 ± 1.12) mmol/L and (8.34 ± 2.34) mmol/L, respectively and they were significantly lower than (6.91 ± 1.86) mmol/L and (10.72 ± 2.48) mmol/L, respectively in the control group ( t = 3.28, 4.76, both P < 0.05). The level of HbAlc was not significant between the two groups ( P > 0.05). The hypoglycemia rate in the observation group was significantly lower than that in the control group [2% (1/48) vs. 13% (6/46), χ2 = 4.09, P < 0.05]. The daily dose of insulin in the observation group was less than that in the control group [(13.5 ± 2.8) IU vs. (15.6 ± 3.1) IU, t = 3.28, P < 0.05)]. Conclusion:Compared with insulin insulin aspart 30, the insulin degludec/insulin aspart has a stronger hypoglycemic effect on fasting plasma glucose level and 2-hour postprandial glucose level in the treatment of type 2 diabetes mellitus in patients with poor efficacy of oral hypoglycemic drugs, leading to a less daily dose of insulin.
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@#Objective To explore the application value of machine learning models in predicting postoperative survival of patients with thoracic squamous esophageal cancer. Methods The clinical data of 369 patients with thoracic esophageal squamous carcinoma who underwent radical esophageal cancer surgery at the Department of Thoracic Surgery of Northern Jiangsu People's Hospital from January 2014 to September 2015 were retrospectively analyzed. There were 279 (75.6%) males and 90 (24.4%) females aged 41-78 years. The patients were randomly divided into a training set (259 patients) and a test set (110 patients) with a ratio of 7 : 3. Variable screening was performed by selecting the best subset of features. Six machine learning models were constructed on this basis and validated in an independent test set. The performance of the models' predictions was evaluated by area under the curve (AUC), accuracy and logarithmic loss, and the fit of the models was reflected by calibration curves. The best model was selected as the final model. Risk stratification was performed using X-tile, and survival analysis was performed using the Kaplan-Meier method with log-rank test. Results The 5-year postoperative survival rate of the patients was 67.5%. All clinicopathological characteristics of patients between the two groups in the training and test sets were not statistically different (P>0.05). A total of seven variables, including hypertension, history of smoking, history of alcohol consumption, degree of tissue differentiation, pN stage, vascular invasion and nerve invasion, were included for modelling. The AUC values for each model in the independent test set were: decision tree (AUC=0.796), support vector machine (AUC=0.829), random forest (AUC=0.831), logistic regression (AUC=0.838), gradient boosting machine (AUC=0.846), and XGBoost (AUC=0.853). The XGBoost model was finally selected as the best model, and risk stratification was performed on the training and test sets. Patients in the training and test sets were divided into a low risk group, an intermediate risk group and a high risk group, respectively. In both data sets, the differences in surgical prognosis among three groups were statistically significant (P<0.001). Conclusion Machine learning models have high value in predicting postoperative prognosis of thoracic squamous esophageal cancer. The XGBoost model outperforms common machine learning methods in predicting 5-year survival of patients with thoracic squamous esophageal cancer, and it has high utility and reliability.
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Objective:To analyze the effects of the main drug resistance mutations in the integrase (IN) region on the resistance of HIV-1 CRF01_AE strains, and compare the differences with subtype B strains.Methods:Seven IN region mutations or combined mutations (T66K, F121Y, Q148K, N155H, G118R, R263K, Q148K/N155H) were selected from the HIV drug resistance database of Stanford University in the United States, and introduced to the IN region of HIV-1 B subtype infectious clone pNL4-3 and CRF01_AE infectious clone pGX002 by seamless cloning, homologous recombination and point mutation. The mutant plasmids were transfected into 293T cells for virus packaging. The culture was expanded in MT2 cells and infectious titers were detected. Half maximal inhibitory concentrations (IC 50) of four integrase inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC), against 14 mutant viruses were detected and compared with the IC 50 against the wild-type viruses. Results:B subtype and CRF01_AE plasmids carrying seven IN region mutations or combined mutations were successfully constructed, and 14 recombinant viruses were packaged with an infectious titer of 10 4-10 6 median tissue culture infective dose (TCID 50)/ml. The recombinant viruses replicated efficiently in MT2 cells. The concentrations of HIV-1 p24 antigen contained in the supernatants of cell culture reached 830-2 700 ng/ml. Five mutations or combined mutations (T66K, F121Y, Q148K, N155H, Q148K/N155H) caused CRF01_AE and B subtype strains to be highly resistant to RAL and EVG, resulting in an increase in the IC 50 by 200 times and 2 000 times or more as compared with the IC 50 against the wild-type viruses. The same mutation-caused fold changes of IC 50 of RAL and EVG against CRF01_AE were significantly lower than that of subtype B ( P<0.01). Q148K/N155H mutation caused B subtype and CRF01_AE to be highly resistant to DTG and BIC, with IC 50 increased by more than 50 times. Other mutations had little effects on the sensitivity to DTG and BIC. Conclusions:Fourteen HIV-1 strains carrying seven INSTI resistance mutations based on B subtype and CRF01_AE were constructed. Five mutations resulted in high resistance to RAL and EVG, and there was a high level of cross-resistance. Resistance to RAL and EVG caused by the same mutation was higher in B subtype than in CRF01_AE. The combined mutation of Q148K and N155H was associated with greater resistance to DTG and BIC, indicating that the genetic barrier of DTG and BIC resistance was high. DTG and BIC could effectively inhibit the strains carrying INSTI resistance mutations without obvious subtype difference.
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[This corrects the article DOI: 10.1016/j.apsb.2021.04.022.].
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Background/Aims@#Metabolic risk factors could accelerate hepatitis B virus (HBV)-related mortality; however, their impacts on disease severity in HBV-related acute on chronic liver failure (HBV-ACLF) patients remain unexplored. In this study, we assessed the effects of metabolic risk factors on the outcome of HBV-ACLF patients. @*Methods@#This study retrospectively enrolled antiviral therapy naïve HBV-ACLF patients from a single center in China. Patients were evaluated according to Child-Turcotte-Pugh score, Model for End-Stage Liver Disease (MELD) score, 30-day, 90-day mortality and survival rate to estimate the prognosis of HBV-ACLF. The impacts of different metabolic risk factors were further analyzed. @*Results@#A total of 233 patients, including 158 (67.8%) with metabolic risk factors and 75 (32.2%) without metabolic risk factors, were finally analyzed. Patients with metabolic risk factors had significantly higher MELD score (22.6±6.1 vs 19.8±3.8, p<0.001), 90-day mortality rate (56.3% vs 38.7%, p=0.017), and shorter median survival time (58 days vs 75 days: hazard ratio, 1.553; 95% confidence interval, 1.061 to 2.274; p=0.036) than patients without them. Moreover, metabolic risk factors were independently associated with patients’ 90-day mortality (hazard ratio, 1.621; 95% confidence interval, 1.016 to 2.585; p=0.043). Prediabetes/diabetes and hypertension were related to higher rates of infection and worse renal function in HBV-ACLF patients. @*Conclusions@#HBV-ACLF patients with metabolic risk factors, especially prediabetes/diabetes or hypertension, could have more severe disease and lower survival rates. In addition, the existence of metabolic disorder is an independent risk factor for HBV-ACLF patients’ 90-day mortality.
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Objective:To investigate the protective effect of hyperbaric oxygen therapy(HBOT)on myocardial fibrosis and oxidative stress induced by D-galactose(D-gal)in senescent model mice and its possible mechanism.Methods:Three-month-old male Kunming mice(n=27)were randomized into control, D-gal, and D-gal + HBOT groups.The control group received subcutaneous sterilized saline(5 ml · kg -1· d -1)for 8 weeks; the remaining 2 groups received subcutaneous D-gal(200 mg · kg -1· d -1)for 8 weeks. The D-gal + HBOT group underwent HBOT intervention at week 7~8.At the end of the experiment, the histopathological changes were analyzed by hematoxylin-eosin(HE)staining, and the fibrosis changes were analyzed by Masson staining and Sirius red staining.Oxidative stress kit was used to detect catalase(CAT), total superoxide dismutase(T-SOD)activity and malon-di-aldehyde(MDA)content in serum of mice.Western blotting was used to detect the expression levels of the aging-related proteins p53 and p16 in mouse heart tissue, the heart-function-related proteins atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP), and the oxidative stress-related protein superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2)and catalase(CAT). Results:Cardiac morphologic staining indicated that as compared with the control group, mice of D-gal group exhibited features of senescence and the increased fibrosis area, and senescence and fibrosis were obviously improved after HBOT intervention as compared with the D-gal group.The findings of the oxidative stress kit measurement indicated that as compared with the control group, the D-gal group had markedly decreased activities of CAT and T-SOD, significantly increased MDA content in the serum.After HBOT treatment, as compared with d-gal group, serum CAT and T-SOD activities were increased, while MDA content was decreased( F=126.85, 32.89, 157.50, all P<0.05).Furthermore, as compared with the control group, the D-gal group had obviously increased contents of p53, p16, ANP and BNP, while the content of CAT, SOD1 and SOD2 were obviously decreased.After HBOT intervention, as compared with the D-gal group, the contents of p53, p16, ANP、BNP were reduced, while the content of CAT, SOD1 and SOD2 were increased( F=36.37, 14.81, 23.28, 58.41, 12.79, 80.08, 6.63, all P<0.05). Conclusions:HBOT intervention could protects against cardiac injury in aging mice, which may be related to attenuating myocardial fibrosis, inducing the expression of antioxidant enzymes, and reducing oxidative stress.
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Objective:To apply knowledge maps to systematically evaluate problem-based learning (PBL) literatures from the past 50 years, so as to explore the law of development and related important documents.Methods:All peer-reviewed studies were retrieved from Web of Science (WOS) Citation Database on PBL of the year from 1970 to 2019. Bibliometrix package of R was used to analyze following items: annual growth law of PBL literature, literature cumulative growth law, literature citation status and top 30 important documents. Based on the results, the law of development of PBL research, important literatures and time nodes was analyzed.Results:After literature cleaning, 2 401 documents were finally included into the analysis. The analysis revealed that: in accordance with the law of development disciplines, PBL study experienced three periods, early birth (Period Ⅰ), PBL study early development (Period Ⅱ) and PBL large-scale development (Period Ⅲ). Now PBL is currently in a period of large-scale development. In the development process, 1983, 1986, 1993, 2003, 2005, 2007, 2011, 2012 and 2014 has become important research time nodes, and there have been five important documents promoting PBL development (ALBANESE MA, 1993, ACAD MED; VERNON DTA, 1993, ACAD MED; NORMAN GR, 1992, ACAD MED; BARROWS HS, 1986, MED EDUC; HMELO-SILVER CE, 2004, EDUC PSYCHOL REV).Conclusion:Nowadays, PBL theory and method has been perfected, which has been developed significantly, and it's an important period of application and promotion. The PBL has become an important method to cultivate clinical skills or other disciplines with strong practicality.
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The window period of HIV infection refers to the time between HIV exposure and quantified and consistent detection of viral markers. The seroconversion window period is the interval between HIV infection and the first detection of antibodies. The eclipse period is the initial phase from HIV infection to reliable detection of HIV RNA. Understanding the window period is the basis for HIV test counseling, helping to provide key information about how soon after HIV exposure the tests and repeat tests should be offered and when the HIV infection can be excluded after negative test results are obtained. It has guiding significance for formulating post-exposure testing algorithm, selecting tests and interpreting test results. This paper introduced the definition of window period, emphasized the main points for accurately understanding the concept, analyzed the factors affecting the window period, especially the impact of antiretroviral drugs on viral marker response and detection, and proposed the follow-up method and post-exposure test strategy based on the length of window period, aiming to provide reference for the diagnosis of acute HIV infection.
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Objective:To develop a questionnaire on perimenopausal cognition and behavior and verify its reliability and validity, in order to provide an effective tool for evaluating perimenopausal women's cognition, doctor-seeking and doctor-following behaviors.Methods:Baseline survey, literature analysis and brainstorming were formed in the initial items, and group discussion and expert interview were performed to identify items of the form. By convenience sampling method, A survey was conducted on perimenopausal women in the communities around Chongqing Health Center for Women and Children from July to August 2019. Project analysis, exploratory factor analysis, confirmatory factor analysis, Pearson correlation analysis and reliability test were used to evaluate the questionnaire.Results:Two rounds of questionnaires were distributed in this study. In the first round, 260 questionnaires were distributed, 249 valid questionnaires were recovered, and the effective recovery rate was 95.8% (249/260). In the second round, 249 questionnaires were distributed, and the effective recovery rate was 96.4% (240/249). The questionnaire on perimenopausal cognition and behavior included 4 dimensions and 24 items. The cumulative contribution of variance was 66.330%, the Cronbach α coefficient was 0.893 and the spearman-brown half-fold coefficient was 0.773. Regarding to the construct validity, the correlation coefficient between factors and total score of the questionnaire was 0.567-0.860 ( P < 0.01). Confirmatory factor analysis showed that the approximate error root mean square was 0.055, the normal fitting index was 0.801, and the goodness of fit index was 0.828. Conclusions:The questionnaire has been proved to be reliable and valid. It can be used to evaluate perimenopausal women′s cognition, doctor-seeking and doctor-following behaviors.
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@#Objective To compare the short-term and long-term effects of minimally invasive esophagectomy (MIE) and traditional open esophagectomy (OE) in patients with stage T1b esophageal squamous cell carcinoma (ESCC). Methods We retrospectively analyzed the clinical pathology data of 162 patients undergoing thoracic surgery at Northern Jiangsu People's Hospital from 2015 to 2018 whose pathological diagnosis was stage pT1b ESCC. According to the surgical approach, they were divided into MIE group and OE group. There were 55 males and 21 females in the OE group, with an average age of 63.3±5.6 years, and 60 males and 26 females in the MIE group, with an average age of 64.7±6.1 years. The preoperative, intraoperative and postoperative data of the two groups were compared and followed up. Survival data were compared using Kaplan-Meier and log-rank tests between the two groups, and Cox proportional hazard regression models were used to analyze prognostic factors. Results Compared with the OE group, the intraoperative bleeding volume of the MIE group was less (119.8±70.0 mL vs. 210.5±136.2 mL, P<0.001), and the lymph nodes dissected during the operation were more (19.1±7.4 vs. 13.8±5.9, P<0.001), the rate of postoperative pulmonary infections was lower (9.3% vs. 21.1%, P=0.036), but the operation time was longer (240.0±52.4 min vs. 179.5±35.7 min, P<0.001). Twenty-one patients had lymph node metastasis, and the lymph node metastasis rate was 13.0%. At the end of the follow-up, 19 patients died, and the overall survival (OS) at 1 year, 3 years, and 5 years after operation were 97.5%, 88.8% and 82.9%, respectively; 31 patients had recurrence and metastasis, and the disease-free survival (DFS) rate at 1 year, 3 years, and 5 years after operation was 95.1%, 80.9% and 75.6%. There was no significant difference in OS and DFS between the two groups. Multivariate Cox regression analysis of OS found that lymph node metastasis, anastomotic fistula and chylothorax were independent risk factors for OS. Multivariate Cox regression analysis of DFS found that lymph node metastasis, anastomotic fistula, chylothorax, and vascular cancer thrombus were independent risk factors for OS. Conclusion MIE can achieve the same long-term effects as OE, with less intraoperative bleeding, more lymph nodes dissected, and lower incidence of postoperative pulmonary infections, but it takes longer operation time.
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Insurmountable blood‒brain barrier (BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease (AD). Poor accumulation of drugs in lesion sites and undesired effectiveness of simply reducing A
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OBJECTIVE：To study the effects and mechanism o f apigenin on cisplatin sensitivity of NSCLC A 549 cells by regulating RAD51 gene. METHODS ：Human lung cancer cisplatin-resistant cells A 549/DDP were selected and divided into control group（blank culture medium ），cisplatin group （5 g/L），apigenin low-dose and high-dose groups （10，20 μmol/L）. MTT assay was used to detect the growth of A 549/DDP cells ，while the Annexin Ⅴ/PI double staining combined with flow cytometry were used to detect the apoptosis. A 549/DDP cells were collected and divided into cisplatin alone group （1，2，4，8，16 μg/mL）， apigenin combination group （10 μmol/L，based on cisplatin ）. MTT method was used to determine and calculate inhibitory rate of cell proliferation. IC 50 values of drugs were calculated by regression model ，and reversion index of apigenin was calculated. 18 nude mice were randomly divided into control group ，cisplatin alone group and apigenin combination group ，with 6 mice in each group. After A 549/DDP cells were inoculated to form the transplanted tumor ，normal saline ，cisplatin（2 mg/kg，once every other day ）， cisplatin（the same dosage and usage ）+apigenin solution （30 mg/kg，once a day ）were injected intraperitoneally respectively. After 18 days of continuous administration ，the body weight of mice and the mass of the transplanted tumor were detected and the tumor inhibition rate was calculated. Human lung cancer cells A 549 and A 549/DDP were collected and divided into normal group （A549 cells），control group （A549/DDP cells ），cisplatin group （5 g/L，A549/DDP cells ）and apigenin low-dose and high-dose groups （10，20 μmol/L，A549/DDP cells ），respectively. mRNA and protein expression of RAD51 were detected by real-time fluorescence quantitative PCR and Western blotting assay. RESULTS ： Δ 基金项目：四川省教育厅（自筹经费）科研项目（No.12ZB227） ＊讲师，硕士。研究方向：肿瘤病理。E-mail：molin212@163.com Compared with control group ，the cell growth of apigenin # 通信作者：副教授，硕士生导师，硕士。研究方向：肿瘤病理。 low-dose and high-dose groups were decreased significantly ， E-mail：xinrongH292@163.com apoptosis rates of them w ere increased significantly and higher ·708· China Pharmacy 2020Vol. 31 No. 6 中国药房 2020年第31卷第6期 than those of cisplat in group （P＜0.05 or P＜0.01）. After combined with apigenin ，proliferation inhibition rate of A 549/DDP cells was increased significantly ，compared with cisplatin alone group with the same concentration （P＜0.05）. The IC 50 in the apigenin combination group was （5.81±0.47）μg/mL，significantly lower than （14.44±0.52）μg/mL in cisplatin alone group（P＜0.05），and reversal index of apigenin was 2.49. The results of nude mice tumor inhibition experiment showed that after combined with apigenin，tumor inhibition rate of A 549/DDP bearing nude mice was 68.72％，significantly lower than 33.82％ in cisplatin alone group. Compared with A 549 cells of normal group ，relative expression of RAD51 mRNA and protein were increased significantly in A549/DDP cells of control group （P＜0.05）. Compared with A 549/DDP cells of control group ，relative expression of RAD51 mRNA and protein in A 549/DDP cells were decreased significantly in apigenin low-dose and high-dose groups （P＜0.05）. Compared with cisplatin group ，relative expression of RAD51 mRNA and protein in A 549/DDP cells of apigenin low-dose and high-dose group were decreased significantly （P＜0.05）. CONCLUSIONS ：Apigenin can effectively reverse drug resistance of cisplatin-resistant A 549/DDP cells in human lung cancer. The mechanism may be related to the reduction of RAD51 gene transcription and protein expression.
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Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.
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@# The concept of enhanced recovery after surgery (ERAS) was firstly demonstrated in practice by the Danish scholar Henrik Kehlet in the early 2000s. At present, the ERAS concept has been widely used in a variety of surgical fields, but its application in esophageal cancer surgery is still limited. The new esophageal ERAS guidelines issued by ERAS Association bring new opportunities for the application and promotion of esophageal cancer surgery. Combined with the current situation of esophageal cancer surgery in China and related literature, in this paper we discuss the specific measures of ERAS concept in perioperative application of esophageal cancer in China.
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@#Objective To investigate the clinical value of 3D CT combined with CT-guided Hookwire for localizing small pulmonary nodules in thoracoscopic pulmonary segmentectomy. Methods From December 2017 to February 2019, 39 patients received thoracoscopic pulmonary segmentectomy in our hospital, including 14 males and 25 females with a mean age of 51.33±11.17 years. Before operation, we used Mimics Medical 20.0 to re-establish the anatomy of lung and locate the small pulmonary nodules with Hookwire guided by CT. Based on the position of Hookwire needle, 3D CT images and simulated surgical methods, thoracoscopic pulmonary segmentectomy was performed accurately. Results The surgery was successfully completed in 39 patients without a transfer to open procedure. The mean operation time, mean intraoperative blood loss, mean postoperative hospital stay, mean thoracic tube drainage time were 148.97±28.56 min, 27.95±17.57 mL, 6.95±1.68 d, 4.21±1.95 d, respectively. Postoperative complications occurred in 5 patients (12.82%), including atrial fibrillation in 1, pulmonary infection in 1, chylothorax in 1, intrathoracic hemorrhage in 1 and pneumothorax in 1. All actual surgical margins were larger than 3.0 cm. Conclusion The application of preoperative 3D CT combined with CT-guided Hookwire to localize small pulmonary nodules is helpful for accurate anatomical segmental resection of the lung, making the operation safe .
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Objective To understand the transmission patterns and risk factors of HIV-1 strain CRF01_AE subtypes in China,and to provide guidance for the implementation of precise intervention.Methods A total of 2 094 CRF01_AE pol sequences were collected in 19 provinces in China between 1996 and 2014.Phylogenetic tree was constructed by PhyML 3.0 software to select the transmission clusters.Transmission network was constructed by Cytoscape 3.6.0,which was further used for exploring of the major risk factors.Results Of the 2 094 sequences,12.18％ (255/2 094) were in clusters.A total of 82 transmission clusters were identified.The numbers of clusters and contained sequences in intra-provincial transmission (61,173) were significantly more than those in inter-provincial transmission (21,82).The ratio of transmission clustering in MSM increased over time from 2.41％ (2/83) during 1996-2008 to 23.61％ (72/305) during 2013-2014,showing a significant upward trend (x2 =27.800,df=1,P =0.000).The proportion of MSM with inter-provincial transmission clusters were higher than those with intra-provincial transmission clusters,which increased from 0.67％ (2/297) during 1996-2008 to 6.36％(30/472) during 2013-2014,showing a significant upward trend (x2=20.276,df=1,P=0.000).The transmission rate in homosexuals of the inter-transmission clusters (86.59％,71/82) was higher than that of intra-provincial transmission clusters (56.65％,98/173),and the difference was statistically significant (x2=22.792,P=0.000).The proportion of inter-provincial transmission clusters with more than 2 transmission routes (33.33％,7/21) was higher than that of intra-provincial clusters (13.11％,8/61),and the difference was statistically significant (x2=4.273,P=0.039).Results from the transmission network analysis indicated that the proportion of high risk population (degree≥4) with inter-provincial transmission clusters (51.22％,42/82) was significantly higher than that with intra-provincial transmission clusters (26.59％,46/173),and the difference was statistically significant (x2=14.932,P=0.000).Inter-provincial clusters were mainly detected in and and MSM.Conclusions Complex transmission networks were found for HIV-1 CRF01_AE strains in the mainland of China.Inter-provincial transmission clusters increased rapidly,MSM played an important role in the wide spread of the strain.More researches in transmission networks are needed to guide the precision intervention.